Inhaled NO is used to treat elevated pulmonary pressures and pulmonary disorders associated with hypoxemia. This method of treatment provides distribution tightly matched to perfusion and local effect because of rapid trapping of inhaled NO by hemoglobin. Moreover, this method of treatment can be readily carried out by an anesthesiologist or a critical care physician who is used to administering gases. Side effects include reaction of NO with oxygen or reactive oxygen species to produce NO2 or other toxic NOx, the toxicity of which is manifested by inflammation, airway hyperactivity, hemorrhage, delay in clinical improvement, renal impairment or death, and reaction with oxyhemoglobin to interfere with its oxygen delivery function, e.g., by forming methemoglobin.
An alternative to inhaled NO gas is nebulized NO donor where the NO donor is present as solid particles or as particles of liquid. This alternative cannot fully avoid the NO2/NOx toxicity problem associated with administration of NO but may produce longer lasting effects than inhaled NO. The distribution in the lungs is according to particle size and is not matched to perfusion so some NO donor deposits in places where it does not reach the blood or small airways. In the general case, these NO compounds have systemic smooth muscle relating effects greater than pulmonary effects, which limit usage for treating pulmonary disorders. Furthermore, this method is not as readily carried out by an anesthesiologist since anesthesiologists do not normally administer aerosols or powders. Moreover, some classes of NO donors have additional toxicities, that is, they possess toxicities that are unrelated to NO, but that are instead related to the group to which NO is attached or from which NO is generated. The disadvantages of administering nebulized NO donor are indicated to be meaningful by the fact that inhaled gaseous NO is approved for use over inhaled liquid or inhaled solid NO-releasing compound.
Use of inhaled NO and use of nitric oxide-releasing compounds inhaled as solids or liquids in an aerosol to treat pulmonary vasoconstriction and asthma are described in Zapol U.S. Pat. No. 5,823,180.